Amphotericin B is a polyene macrolide compound having antifungal properties. It is produced by cultivation of an organism and extracted from the culture. Amphotericin B is essentially a high molecular weight macrocyclic lactone, better known as a macrolide, possessing a chromophore of 7 conjugated double bonds. In addition to the large lactone nucleus, amphotericin B has other characteristic groups including an amino sugar. A general discussion of macrolide antibiotics is found in Kirk-Othmer, Encyclopedia of Chemical Technology, Second Edition, Volume 12, pp. 632 et seq., while a general discussion of polyene antibiotics is found in the same work, Volume 16, pp. 133 et seq.
While amphotericin B has been recognized as a valuable material, particularly in its powerful antifungal properties and in the apparent inability of fungus organisms to develop readily any strains or forms that are resistant to amphotericin B, its use has been limited by lack of adequate water solubility in forms of amphotericin B which are otherwise stable and appropriate.
Schaffner et al., Antibiotics and Chemotherapy, Vol. XI, No. 11, 724-732 disclose the preparation of N-acylamphotericin B, such as N-succinylamphotericin B, by reaction of succinic anhydride with a slurry of amphotericin B in methanol whereby the anhydride reacts with the amino groups of the amphotericin B. Although Schaffner et al indicate that certain of the N-acylamphotericin B exhibit increased solubility in organic solvents and that acidic derivatives, as their alkaline salts, exhibit true water solubility, unfortunately, it has been found that N-succinylamphotericin B has only about 2-3% of the in vitro bioactivity of the parent amphotericin B and such N-succinyl derivative has an in vivo bioactivity proportional to its in vitro activity. Accordingly, it is quite clear that the N-succinylamphotericin B is inferior in biological activity to the parent amphotericin B.